The complex relationship between humans and their microbiome and the changes of the microbiome during onset of human disease are poorly understood. We propose to form a multiomics Center for the detailed longitudinal analysis of both the microbiome, its activity, and its interconnected relationship with the host during healthy and disease states by omics profiling. Building upon our broad expertise, we will analyze several human microbiomes (fecal, nasal, and exogenous viral) in conjunction with host blood and urine components. Samples will be collected and analyzed during healthy and viral infections from the same individuals over the course of at least three years. Through analysis ofthe microbiome and host biological activities as measured through a variety of omics approaches (metagenome, genome, transcriptome, proteome, metabolome), we will follow the dynamic changes in the microbiome and host pathways that occur during viral infections and other potential stresses, and obtain an unprecedented view ofthe molecular pathways that change during this period. We will focus on subjects at risk for diabetes, and we will correlate the molecular changes in microbiome (endogenous and viral) activity with changes in host glucose levels and diabetes onset. Overall, more than 1080 different physiological states will be analyzed in omic detail and the microbiome and corresponding host information will be deposited in a public repository and serve as an invaluable resource to the scientific community. To accomplish this goal we have assembled a uniquely qualified team.